It is now believed that the hydrolysis of proteins to amino acids in the digestive tract is practically complete. The significance of this digestive cleavage lies not simply in the formation of more soluble and more readily diffusible substances, but also in the resolution of the complex molecules of food protein into their simple amino acid "building stones" ("Bau-steine") which may be rearranged by the body in the synthesis of its own tissue proteins.

* Phlorizin causes very great glycosuria and, if the poisoning is continued, the usual symptoms of severe diabetes such as muscular weakness, acidosis, acetonuria, and death in coma. From moderate dosage, however, the animal recovers. The glucose content of the blood falls (instead of rising as in true diabetes). The action of the phlorizin appears to be primarily upon the kidneys, causing them to secrete glucose much more rapidly than usual, thus draining off the glucose from the blood and keeping it below the normal level.

Absorption And Distribution Of Protein Digestion Products

The work of the past few years, to be described in the paragraphs which follow, indicates that the amino acids, resulting from digestive hydrolysis of the food proteins, pass through the intestinal wall and into the blood of the portal vein unchanged, are carried through the liver into the blood of the general circulation and are thus distributed throughout the body, and are rapidly absorbed from the blood into the various tissues. Thus each tissue receives its protein material in the form of amino acids from which can be synthesized the particular kind of protein characteristic of the tissue in question. In other words, each tissue makes its own proteins from the amino acids brought by the blood. Amino acids not used in synthesizing protein (whether brought by the blood or formed by breakdown of tissue material) are broken down or deaminized in the tissues in the manner described beyond.

A brief account of recent work on the distribution and immediate fate of the amino acids may serve to give a more adequate impression of the modern view.

In 1906 Howell obtained a qualitative reaction for amino acids in the blood, but conclusive evidence of the relation of these amino acids to metabolism required the development of better methods than were then available for the estimation of amino acid nitrogen in the fluids and tissues of the body. Such methods were developed and applied independently and almost simultaneously in 1912 by Folin and Denis and by Van Slyke and Meyer.

Folin and Denis distinguished between the nitrogen of proteins, non-proteins, ammonia, and urea. The non-protein nitrogen includes that of amino acids and they were able to show that this form of nitrogen increased in the blood and tissues when glycine or a mixture of amino acids resulting from pancreatic digestion of protein was undergoing absorption from the small intestine. Moreover the increase in the nonprotein nitrogen of the blood and muscles was nearly sufficient to account for the nitrogenous material absorbed from the intestine, from which it appeared that they had traced the absorbed amino acids and found them to be carried through the blood and to the muscles without being either built up into protein or broken down into ammonia or urea on the way. Urea formation was found to follow distinctly later than the absorption and distribution of the amino acids.

Van Slyke and Meyer estimated amino acids by quantitative determination of the nitrogen present as amino groups in the non-protein fraction of the blood or tissue. They found that, during the digestion of protein, amino acids pass through the intestinal wall and appear not only in the portal blood but also in the blood of the general circulation, showing that the amino acids, for the most part at least, pass both the intestinal wall and the liver unchanged.

Closely following the work of Folin and of Van Slyke, Rona (1912) demonstrated by experiments upon isolated segments of intestine that the amino acids pass unchanged through the intestinal wall; Abel (1913) dialyzed free amino acids from the circulating blood of living animals by means of his vivi-diffusion apparatus and actually separated alanine in crystalline form; and Abderhalden (1914) separated glycine, alanine, valine, leucine, aspartic acid, glutamic acid, lysine, arginine, histidine, and tryptophane from large quantities of shed blood. Soon afterward (1915) Henriques and Andersen showed that dogs and goats could be kept in a normal condition of nutrition and might even store nitrogen and gain weight when they were nourished exclusively by intravenous injection of a food solution containing nitrogen only in the form of completely digested protein - a strong confirmation both of the completeness of cleavage of protein in normal digestion and of the fact that the body is nourished by free amino acids carried by the blood without intervention of chemical changes in the intestinal wall.

Van Slyke (working upon dogs) continued his investigation of the fate of the amino acids and found that they are rapidly taken up from the blood by the tissues where they seem to be held by adsorption. Since the amino acids can be extracted by means of cold water or alcohol they do not seem to be held in chemical combination with the tissue proteins nor can simple diffusion account for the extent to which they enter the tissues, because they rapidly attain a higher concentration in the muscle and liver cells than in the blood with which these are in contact. The extent to which this concentration of amino acids in the muscles may go seems to have a fairly definite limit at about 75 milligrams of amino acid nitrogen per 100 grams of muscle. In the case of liver tissue this "saturation capacity" seems somewhat more elastic and the concentration may reach about twice the maximum observed in muscle, i.e. up to 150 milligrams of amino acid nitrogen per 100 grams of liver. In the muscles the amino acids taken up as just described disappear only very gradually and may not seem to be appreciably changed for several hours; in the liver they disappear rapidly; in the kidney, pancreas, and spleen they disappear less rapidly than in the liver.

The disappearance of the amino acids from the tissues may be due either to a building up into protein or a breaking down with the formation of ammonia and urea or both. It seems probable that in general both processes go on in all tissues, each tissue building its own proteins and each also taking part in the deaminization of amino acids with formation of ammonia or urea. The more rapid disappearance of amino acids from the liver tissue is probably due to the greater activity of the liver in deaminization and urea formation, especially since Van Slyke has recently measured the increase of urea in the blood on its passage through the liver and shown that the passage of the blood through the muscle under parallel conditions does not increase its urea content to a measurable extent.

Van Slyke's experiments also show that the blood contains amino acids at all times and that the tissues are not freed from amino acids by fasting, while on the other hand high protein feeding does not result in any great accumulation of amino acids as such either in the blood or tissues. All these observations confirm the view that amino acids are the normal intermediary products in both the building up and breaking down of body protein and that any large storage of nitrogen in the body must be due to formation of body protein and not to mere accumulation of free amino acids.